Ultramodern Underground Dallas: Vincent Ponte’s Pedestrian-Way as Systematic Solution to the Declining Downtown

Mid last century, North American civil servants and urban planners and developers proffered inventive solutions to the problem of the declining downtown core. Robert Moses looked to super-block development and Title 1 of the US Housing Act of 1949 to funnel federal dollars into urban renewal projects in New York City. Because it had been successful in the suburbs, Victor Gruen sought retail development in the form of downtown shopping centres. The Montreal-based planner Vincent Ponte focused his attention on the “multi-level city centre.” Similar to the solutions proffered by Gruen and Moses, Ponte’s multi-level centres were large-scale and multi-use. However, unlike his colleagues’ tabula rasa interventions, Ponte’s multi-level centre was incremental. This essay focuses on Ponte’s little-known 1969 multi-level pedestrian-way plan for downtown Dallas. I argue that Ponte’s project for the centre of Dallas is unique in Ponte’s oeuvre because, departing from his own espousal of super-block development, it was not built in one fell swoop within a super-block. The multi-level megastructural pedestrian-way in Dallas was fluid and incremental in its original planning and subsequent evolution. It is best understood according to Ponte’s instrumentalization of systems theory.Au milieu du siècle dernier, les fonctionnaires ainsi que les urbanistes et promoteurs d’Amérique du Nord ont présenté diverses solutions novatrices en vue de résoudre le déclin du centre-ville. Robert Moses s’est tourné vers l’aménagement de méga-îlots de même que vers le Titre 1 de la US Housing Act de 1949, afin de canaliser des fonds du gouvernement fédéral dans des projets de rénovation urbaine à New York. Par suite du succès de la formule dans les banlieues, Victor Gruen a visé l’essor du secteur de la vente au détail au moyen de la construction de centres commerciaux au centre-ville. Pour sa part, le planificateur montréalais Vincent Ponte a axé ses efforts sur les centres de ville aux multiples niveaux. Similaires aux solutions offertes par Gruen et Moses, les centres multiniveaux de Ponte étaient d’envergure et à usages multiples. Toutefois, contrairement à l’approche de la table rase de ses confrères, le centre multiniveau de Ponte était de nature incrémentale. Le présent article porte sur un projet peu connu de Ponte, élaboré en 1969, pour une voie piétonne multiniveau destinée au centre-ville de Dallas. Je soutiens que ce projet est unique dans l’oeuvre de Ponte en ce qu’il délaisse sa propre notion de méga-îlot et que la structure n’a pas été construite en une seule fois. La voie piétonne à multiple niveaux à Dallas a bénéficié, dès l’origine, d’une conception pour une construction et une évolution par étapes. Le projet s’analyse le mieux selon l’instrumentalisation qu’a fait Ponte de la théorie des systèmes

HDAC inhibition potentiates immunotherapy in triple negative breast cancer.

Triple-negative breast cancer (TNBC) represents a more aggressive and difficult subtype of breast cancer where responses to chemotherapy occur, but toxicity is significant and resistance often follows. Immunotherapy has shown promising results in various types of cancer, including breast cancer. Here, we investigated a new combination strategy where histone deacetylase inhibitors (HDACi) are applied with immune checkpoint inhibitors to improve immunotherapy responses in TNBC. Testing different epigenetic modifiers, we focused on the mechanisms underlying HDACi as priming modulators of immunotherapy. Tumor cells were co-cultured with human peripheral blood mononuclear cells (PBMCs) and flow cytometric immunophenotyping was performed to define the role of epigenetic priming in promoting tumor antigen presentation and immune cell activation. We found that HDACi up-regulate PD-L1 mRNA and protein expression in a time-dependent manner in TNBC cells, but not in hormone responsive cells. Focusing on TNBC, HDACi up-regulated PD-L1 and HLA-DR on tumor cells when co-cultured with PBMCs and down-regulated CD4+ Foxp3+ Treg in vitro. HDACi significantly enhanced the in vivo response to PD-1/CTLA-4 blockade in the triple-negative 4T1 breast cancer mouse model, the only currently available experimental system with functional resemblance to human TNBC. This resulted in a significant decrease in tumor growth and increased survival, associated with increased T cell tumor infiltration and a reduction in CD4+ Foxp3+ T cells in the tumor microenvironment. Overall, our results suggest a novel role for HDAC inhibition in combination with immune checkpoint inhibitors and identify a promising therapeutic strategy, supporting its further clinical evaluation for TNBC treatment

Sexually dimorphic role for vasopressin in the development of social play

Despite the well-established role of vasopressin (AVP) in adult social behavior, its role in social development is relatively unexplored. In this paper, we focus on the most prominent social behavior of juvenile rats, social play. Previous pharmacological experiments in our laboratory suggested that AVP regulates play in a sex- and brain region-specific manner in juvenile rats. Here we investigate the role of specific AVP systems in the emergence of social play. We first characterize the development of play in male and female Wistar rats and then ask whether the development of AVP mRNA expression correlates with the emergence of play. Unexpectedly, play emerged more rapidly in weanling-aged females than in males, resulting in a sex difference opposite of that typically reported for older, juvenile rats. AVP mRNA and play were correlated in males only, with a negative correlation in the bed nucleus of the stria terminalis and a positive correlation in the paraventricular nucleus of the hypothalamus. These findings support the hypothesis that AVP acts differentially on multiple systems in a sex-specific manner to regulate social play and suggest a role for PVN and BNST AVP systems in the development of play. Differential neuropeptide regulation of male and female social development may underlie well-documented sex differences in incidence, progression, and symptom severity of behavioral disorders during development

Interaction between Streptococcus pneumoniae and Staphylococcus aureus in paediatric patients suffering from an underlying chronic disease

Little is known about the interaction between Streptococcus pneumoniae and Staphylococcus aureus in school-age children and adolescents suffering from an underlying chronic disease. To increase our knowledge in this regard, an oropharyngeal swab was obtained from school-age children and adolescents suffering from asthma (n = 423), cystic fibrosis (CF) (n = 212) and type 1 diabetes mellitus (DM1) (n = 296). S. pneumoniae detection and serotyping were performed using a real-time polymerase chain reaction, and S. aureus detection was performed using the RIDAGENE MRSA system. Among asthmatic, CF and DM1 patients, both pathogens were identified in 65/423 (15.4%), 21/212 (9.9%) and 62/296 (20.9%) children, respectively; S. pneumoniae alone was identified in 127/434 (30.0%), 21/212 (9.9%) and 86/296 (29.1%), respectively; S. aureus alone was identified in 58/434 (13.7%), 78/212 (36.8%) and 49/296 (16.6%), respectively. S. pneumoniae colonisation rates were higher in younger children and declined with age, whereas the frequency of S. aureus colonisation was quite similar in the different age groups. Among asthmatic and CF patients aged 6-9 years, S. aureus carriage was significantly higher in children who were positive for S. pneumoniae (P <0.05). No significant association emerged between S. aureus carriage and carriage of S. pneumoniae serotypes included in the pneumococcal conjugate vaccines (PCVs). This study shows for the first time that school-age children and adolescents with asthma, CF and DM1 are frequently colonised by S. pneumoniae and S. aureus and that no negative relationship seems to exist between these pathogens. Moreover, the supposed protection offered by PCV administration against S. aureus colonisation was not demonstrated

A compact light readout system for longitudinally segmented shashlik calorimeters

The longitudinal segmentation of shashlik calorimeters is challenged by dead zones and non-uniformities introduced by the light collection and readout system. This limitation can be overcome by direct fiber-photosensor coupling, avoiding routing and bundling of the wavelength shifter fibers and embedding ultra-compact photosensors (SiPMs) in the bulk of the calorimeter. We present the first experimental test of this readout scheme performed at the CERN PS-T9 beamline in 2015 with negative particles in the 1-5~GeV energy range. In this paper, we demonstrate that the scheme does not compromise the energy resolution and linearity compared with standard light collection and readout systems. In addition, we study the performance of the calorimeter for partially contained charged hadrons to assess the $e/\pi$ separation capability and the response of the photosensors to direct ionization.Comment: To appear in Nuclear Instruments and Methods in Physics Research,

Molecular dynamics simulation for baryon-quark phase transition at finite temperature and density

We study the baryon-quark phase transition in a molecular dynamics (MD) of quark degrees of freedom at finite temperature and density. The baryon state at low density and temperature, and the deconfined quark state at high density and temperature are reproduced. We investigate the equations of state of matters with different $u$-$d$-$s$ compositions. Then we draw phase diagrams in the temperature-density plane by this simulation. It is found that the baryon-quark transition is sensitive to the quark width.Comment: submitted to EPJ

Architects of time: Labouring on digital futures

Drawing on critical analyses of the internet inspired by Gilles Deleuze and the Marxist autonomia movement, this paper suggests a way of understanding the impact of the internet and digital culture on identity and social forms through a consideration of the relationship between controls exercised through the internet, new subjectivities constituted through its use and new labour practices enabled by it. Following Castells, we can see that the distinction between user, consumer and producer is becoming blurred and free labour is being provided by users to corporations. The relationship between digital technologies and sense of community, through their relationship to the future, is considered for its dangers and potentials. It is proposed that the internet may be a useful tool for highlighting and enabling social connections if certain dangers can be traversed. Notably, current remedies for the lack of trust on the internet are questioned with an alternative, drawing on Zygmunt Bauman and Georg Simmel, proposed which is built on community through a vision of a ‘shared network’

Photonuclear reactions of actinides in the giant dipole resonance region

Photonuclear reactions at energies covering the giant dipole resonance (GDR) region are analyzed with an approach based on nuclear photoabsorption followed by the process of competition between light particle evaporation and fission for the excited nucleus. The photoabsorption cross section at energies covering the GDR region is contributed by both the Lorentz type GDR cross section and the quasideuteron cross section. The evaporation-fission process of the compound nucleus is simulated in a Monte-Carlo framework. Photofission reaction cross sections are analyzed in a systematic manner in the energy range of $\sim$ 10-20 MeV for the actinides $^{232}$Th, $^{238}$U and $^{237}$Np. Photonuclear cross sections for the medium-mass nuclei $^{63}$Cu and $^{64}$Zn, for which there are no fission events, are also presented. The study reproduces satisfactorily the available experimental data of photofission cross sections at GDR energy region and the increasing trend of nuclear fissility with the fissility parameter $Z^2/A$ for the actinides.Comment: 4 pages including 2 tables and 1 figur

Genetic polymorphisms and sepsis in premature neonates

Identifying single nucleotide polymorphisms (SNPs) in the genes involved in sepsis may help to clarify the pathophysiology of neonatal sepsis. The aim of this study was to evaluate the relationships between sepsis in pre-term neonates and genes potentially involved in the response to invasion by infectious agents. The study involved 101 pre-term neonates born between June 2008 and May 2012 with a diagnosis of microbiologically confirmed sepsis, 98 pre-term neonates with clinical sepsis and 100 randomly selected, otherwise healthy pre-term neonates born during the study period. During the study, 47 SNPs in 18 candidate genes were genotyped on Guthrie cards using an ABI PRISM 7900 HT Fast real-time and MAssARRAY for nucleic acids instruments. Genotypes CT and TT of rs1143643 (the IL1\u3b2 gene) and genotype GG of rs2664349GG (the MMP-16 gene) were associated with a significantly increased overall risk of developing sepsis (p = 0.03, p = 0.05 and p = 0.03), whereas genotypes AG of rs4358188 (the BPI gene) and CT of rs1799946 (the DEF\u3b21 gene) were associated with a significantly reduced risk of developing sepsis (p = 0.05 for both). Among the patients with bacteriologically confirmed sepsis, only genotype GG of rs2664349 (the MMP-16 gene) showed a significant association with an increased risk (p = 0.02). Genotypes GG of rs2569190 (the CD14 gene) and AT of rs4073 (the IL8 gene) were associated with a significantly increased risk of developing severe sepsis (p = 0.05 and p = 0.01). Genotype AG of rs1800629 (the LTA gene) and genotypes CC and CT of rs1341023 (the BPI gene) were associated with a significantly increased risk of developing Gram-negative sepsis (p = 0.04, p = 0.04 and p = 0.03). These results show that genetic variability seems to play a role in sepsis in pre-term neonates by influencing susceptibility to and the severity of the disease, as well as the risk of having disease due to specific pathogens. \ua9 2014 Esposito et al